Systemic diseases as varied as diabetes, renal failure and rheumatoid arthritis can affect the healing of lower extremity wounds. When it comes to treating chronic wounds, there is an array of testing one can employ to rule out systemic disease as a potential cause. There are also key warning signs that may indicate a possible malignancy. With these issues in mind, our multidisciplinary panel offered the following insights. Q: What are the most common systemic diseases that manifest themselves as lower extremity wounds? A: Diabetes is a common finding for Michael S. Miller, DO, Richard Schlanger, MD, and Lawrence Karlock, DPM. Drs. Karlock and Miller also see lower-extremity wounds in patients with sickle cell anemia and rheumatoid arthritis, and Dr. Miller also sees seronegative arthritis in patients. Dr. Miller also sees conditions including inflammatory bowel disease, hematologic malignancies, autoimmune conditions such as lupus, collagen vascular disease and vasculitis. For Dr. Schlanger, the most common systemic diseases manifesting in lower extremity wounds are vascular conditions like venous disease, peripheral vascular disease and collagen vascular disease. He also sees AIDS, IV drug use and end-stage renal disease. He notes that many of those conditions “meld together in a collage of comorbidities.” Dr. Karlock adds that he encounters patients with pyoderma gangrenosum and sarcoidosis that manifest as lower extremity wounds. Q: When patients present with a chronic, non-healing wound, what workup do you perform to rule out a systemic cause? A: For patients with lower extremity ulcers and non-healing wounds, Dr. Schlanger orders a multi-stage workup. This entails blood work, including CBC, SMA 7, HbA1c, pre-albumin and erythrocyte sedimentation rate testing. As he notes, these basic tests will indicate one or more systemic problems that have caused a derailment in the healing cascade. Dr. Miller will likewise use a CBC test and also utilizes renal and hepatic function tests, lower intestinal endoscopy and chest X-rays. While noting that no single diagnostic test is definitive, he says the aforementioned tests can be helpful. Dr. Miller will also obtain a bone marrow biopsy. However, for a condition such as pyoderma gangrenosum, Dr. Miller cautions that a biopsy of the wound itself may exacerbate the condition. Therefore, when it comes to patients with suspected pyoderma gangrenosum, he says one would make the diagnosis and exclude other causes by assessing the clinical presentation. Like Dr. Schlanger, Dr. Karlock will use an HbA1c comprehensive metabolic test, depending on the patient’s clinical picture. If he has any questions about an undiagnosed, underlying systemic cause, he refers patients to an internist for a workup. To determine a vascular baseline, Dr. Schlanger will use TcPO2 testing, saying he can test without using a wound clinic and can interpret the results immediately. The readings from the TcPO2 test will provide insight into the cutaneous blood flow and possible inflow problems, which may require more invasive testing. He notes Doppler studies can help rule out blockages. Q: What signs warn you of a possible malignancy in a chronic foot or ankle wound? A: Taking a biopsy is key to identifying a malignant wound, according to Drs. Miller and Schlanger. However, Dr. Miller notes the trick is knowing when to biopsy. One would biopsy a wound that continues to get worse despite appropriate therapy and also has a negative systemic workup, advises Dr. Miller. Dr. Schlanger says one should biopsy a wound that has not responded after 30 days of treatment. He adds that one should include the lesion and normal skin for a biopsy or else the pathologist is merely considering the inflamed cells of the wound. Dr. Karlock concurs. He says clinicians should have a higher index of suspicion for malignancy when dealing with wounds that have not responded to conventional therapy and wounds that have growing or spreading lesions with irregular borders. In addition, Dr. Miller notes a wound that recurs after apparent healing warrants a biopsy and a patient with a history of skin or soft tissue malignancies is at risk for recurrence. Recently, he treated a patient with multiple ulcerated lesions on her fingers and hands, and the patient had previously had a squamous cell carcinoma of the arm removed. Her biopsies showed these hand lesions were squamous cell carcinoma as well, according to Dr. Miller. Q: Do you have any special concerns or pearls for treating the renal failure patient with a chronic wound? What about treating rheumatoid arthritic patients with lower extremity wounds? A: Dr. Schlanger has experienced the most problems with his renal failure patients, saying he finds calciphylaxis very difficult to treat. In these cases, he says it is important to keep the lesion clean and avoid debridement unless it is necessary. Managing the calcium level in the wound will keep the lesion self-contained and facilitate eventual healing, according to Dr. Schlanger. He emphasizes control of edema and infection through effective dialysis and early recognition of cellulitis. When treating patients with renal failure, Dr. Miller has noted generalized pruritus, which he calls “severe and unrelenting.” He says this leads to multiple severe wounds and cellulitis due to scratching. If anti-pruritic medications do not work, Dr. Miller will order a systemic workup to rule out other causes. The goal of treatment, according to Dr. Miller, is minimizing the potential for more trauma while permitting the healing of the injured tissue. “In other words, the goal is to treat the cause which, in this case, is self-trauma,” he notes. Dr. Miller will use a zinc oxide impregnated gauze wrap (Unna’s Boot) to protect the injured skin from the traumatizing fingers. He applies multiple layers of the wrap and covers it with a cohesive bandage. Dr. Miller says he leaves the wrap on for a week and then reapplies it. When the ZnO2 layers fit snugly with the skin, Dr. Miller says the layers prevent patients from getting into the wraps, adding that even if they rub the outside of the wrap to scratch, the resultant trauma is still reduced. For these patients, Dr. Miller will also consider using topical steroids under the wraps and adjunctive use of anti-pruritic medications. “The end stage renal patient with diabetes is a notoriously poor candidate for lower extremity wound healing,” adds Dr. Karlock. “Even under the best of circumstances, these patients seem to poorly heal these wounds.” As for rheumatoid arthritis, Dr. Schlanger has found steroids and other chemotherapy agents work against wound healing. He splints the extremity, uses padding to prevent further breakdown and cautions that patients need to maintain nutrition to promote healing. “These patients are fragile and need to be handled very carefully,” advises Dr. Schlanger. Q:What systemic factors negatively affect wound healing? A: All three panelists cite diabetes as a negative factor with Dr. Schlanger noting that patients cannot heal until they have good glucose control. Drs. Karlock and Miller cite malnutrition and anemia for their affects on wound healing. Drs. Karlock and Schlanger also cite nicotine abuse. Smoking, alcohol and drug abuse all inhibit the body’s healing ability due to hypoxia and vasoconstriction or malnutrition and liver damage, according to Dr. Schlanger. He adds that steroids and chemotherapy are cytotoxic and can disrupt healing. Dr. Miller also adds inadequate perfusion and metabolic abnormalities to the list of factors that negatively affect wound healing. However, he notes such factors are “virtually endless” and include the systemic effects of bodily systems, including hepatic and renal systems. “Suffice it to say that you need to search for not just the cause of a chronic wound but related healing-inhibitory factors,” notes Dr. Miller. Dr. Miller is certified in chronic wound management and board certified in general surgery. He is the Medical Director of four wound healing centers in Indiana. Dr. Schlanger is the Director of the Ohio State University Wound Healing Center at University Hospital East. He is a Fellow of the American College of Surgery. Dr. Karlock is a Fellow of the American College of Foot and Ankle Surgeons, and practices in Austintown, Ohio. He is a member of the Editorial Advisory Board for WOUNDS, a Compendium of Clinical Research and Practice.